Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University , Nanjing, Jiangsu, China.
National Institute of Clinical Drug Trials, The First Affiliated Hospital of Bengbu Medical University , Bengbu, Anhui, China.
Expert Opin Drug Metab Toxicol. 2020 Oct;16(10):997-1003. doi: 10.1080/17425255.2020.1807935. Epub 2020 Aug 26.
This study aimed to evaluate the bioequivalence, safety, tolerability and immunogenicity of the biosimilar trastuzumab (SIBP-01) compared to Herceptin®.
In this Phase I randomized double-blind parallel-group trial, 100 healthy male volunteers were randomized in a1:1 ratio to receive a single 6 mg•kg-1 intravenous dose of SIBP-01 or Herceptin®. Serum concentrationswere analyzed using a validated ELISA.
The two groups had similar baseline characteristics. The geometric mean ratios (90% CI) of C, AUC and AUC between the trial group and the reference group were 93.55%-104.27%, 91.98%-102.35% and 91.88%-102.34%, respectively; the geometric mean ratios (90% CI) of AUC and AUC in the sensitivity analysis were 92.29%-102.63% and 91.81%-102.16%, respectively. These values were within the prespecified equivalence margins, establishing the bioequivalence of SIBP-1 and Herceptin®. AEs were similar across all subjects in the SIBP-01 and Herceptin® arms, with treatment-related AEs reported by 72.00% and 80.00%, respectively. In each group, there was one AE that caused a subject to discontinue the study.
Trastuzumab (Herceptin®) is significantly more effective than chemotherapy in reducing exacerbations and tumor cell growth, and its adverse events are far lower than chemotherapy. Herceptin®is very expensive for most patients in China. The protein molecular primary structure of the biosimilar trastuzumab (SIBP-01) is consistent with Herceptin®, with highly similar high level structure, biologocal activity and purity.But there are few studies comparing the bioequivalence of SIBP-01 and Herceptin® in healthy subjects and cancer patients 2.
This study showed the PK similarity of SIBP-01 to Herceptin®. SIBP-01 was safe and well tolerated in healthy male volunteers, with no significant differences from the reference drug in safety or immunogenicity 4.
本研究旨在评估与赫赛汀®相比，生物类似药曲妥珠单抗（SIBP-01）的生物等效性、安全性、耐受性和免疫原性。
在这项 I 期随机双盲平行组试验中，将 100 名健康男性志愿者按照 1:1 的比例随机分为两组，分别接受单次 6mg•kg-1 静脉注射 SIBP-01 或赫赛汀®。采用经过验证的 ELISA 法分析血清浓度。
两组具有相似的基线特征。试验组与参比组的 C、AUC 和 AUC 的几何均数比值（90%CI）分别为 93.55%-104.27%、91.98%-102.35%和 91.88%-102.34%；敏感性分析中 AUC 和 AUC 的几何均数比值（90%CI）分别为 92.29%-102.63%和 91.81%-102.16%。这些值均在预设的等效性范围内，证实了 SIBP-1 与赫赛汀®的生物等效性。SIBP-01 组和赫赛汀®组的所有受试者的不良事件（AE）相似，分别有 72.00%和 80.00%的受试者报告了与治疗相关的 AE。在每组中，均有 1 例 AE 导致受试者退出研究。
曲妥珠单抗（赫赛汀®）在减少恶化和肿瘤细胞生长方面明显优于化疗，其不良反应远低于化疗。对于大多数中国患者来说，赫赛汀®非常昂贵。生物类似药曲妥珠单抗（SIBP-01）的蛋白质分子一级结构与赫赛汀®一致，具有高度相似的高级结构、生物学活性和纯度。但比较 SIBP-01 与赫赛汀®在健康受试者和癌症患者中的生物等效性的研究较少。
本研究表明 SIBP-01 的 PK 与赫赛汀®相似。SIBP-01 在健康男性志愿者中安全且耐受良好，与参比药物在安全性或免疫原性方面无显著差异。
